Deficiency of urokinase plasminogen activator may impair β cells regeneration and insulin secretion in type 2 diabetes mellitus

Chung Ze Wu, Shih Hsiang Ou, Li Chien Chang, Yuh Feng Lin, Dee Pei, Jin Shuen Chen

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Background: The relationship between urokinase-type plasminogen activator (uPA) and the development of type 2 diabetes mellitus (T2DM) was investigated in the study by using mice and cell models, as well as patients with T2DM. Methods: In mice models, wild-type and uPA knockout (uPA-/-) BALB/c mice were used for induction of T2DM. In cell models, insulin secretion rate and β cell proliferation were assessed in normal and high glucose after treating uPA siRNA, uPA, or anti-uPA antibody. In our clinical study, patients with T2DM received an oral glucose-tolerance test, and the relationship between uPA and insulin secretion was assessed. Results: Insulin particles and insulin secretion were mildly restored one month after induction in wild-type mice, but not in uPA-/-mice. In cell models, insulin secretion rate and cell proliferation declined in high glucose after uPA silencing either by siRNA or by anti-uPA antibody. After treatment with uPA, β cell proliferation increased in normal glucose. In clinical study, patients with T2DM and higher uPA levels had better ability of insulin secretion than those with lower uPA levels. Conclusion: uPA may play a substantial role in insulin secretion, β cell regeneration, and progressive development of T2DM. Supplementation of uPA might be a novel approach for prevention and treatment of T2DM in the future.

Original languageEnglish
Article number4208
JournalMolecules
Volume24
Issue number23
DOIs
Publication statusPublished - Nov 20 2019

Keywords

  • Insulin secretion
  • Type 2 diabetes mellitus
  • Urokinase plasminogen activator
  • β cell regeneration

ASJC Scopus subject areas

  • Analytical Chemistry
  • Chemistry (miscellaneous)
  • Molecular Medicine
  • Pharmaceutical Science
  • Drug Discovery
  • Physical and Theoretical Chemistry
  • Organic Chemistry

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